Project Summary/Abstract The subjective experience of pain is constructed and modulated by a constellation of interactions between sensory, cognitive and affective factors. These dimensions render the efficacious treatment of chronic pain to be challenging and has led to the exponential growth in opioid misuse and the so-called ?opioid epidemic?. Chronic pain is pervasive and a major financial burden affecting over 100 million Americans and costs the United States approximately $635 billion dollars a year. These staggering statistics highlight the importance of developing, testing and validating fast-acting, non-pharmacological approaches to treat pain. Mindfulness meditation is a technique that significantly reduces pain in experimental and clinical settings. However, lack of mechanistic data and the assumption that extensive meditation training is required to experience analgesia has limited the clinical deployment of this cost-effective and narcotic-free treatment. Recent findings from our laboratory determined that mindfulness meditation, after only four, 20-minute training sessions, dramatically reduces pain. Yet, mindfulness meditation likely engages a number of non-specific factors (conditioning; demand characteristics) associated with placebo responses. To this extent, it is critical that we disentangle and identify the specific pain-relieving mechanisms supporting mindfulness. We have developed and validated a novel comparison condition characterized as sham-mindfulness meditation that operationally resembles mindfulness meditation. Our prior work revealed that mindfulness meditation is more effective than and engages distinct neural mechanisms from sham-mindfulness meditation to reduce pain. We also recently discovered that mindfulness-based pain reductions were not mediated by the release of endogenous opioids. These findings show that mindfulness meditation reduces pain through multiple, unique processes that are independent from the analgesic mechanisms supporting placebo. However, said results cannot be explicitly generalized to chronic pain patients because they were conducted in healthy, pain-free participants using noxious heat to induce pain. This point is critical because chronic pain patients exhibit a significant deficiency in endogenous opioidergic functioning, potentially reflecting the inability to regulate pain. Importantly, the role of endogenous opioids in the modulation of chronic pain by mindfulness meditation remains unknown. The central aim of the proposed double blind, crossover randomized study is to determine if mindfulness meditation attenuates acutely evoked chronic low back pain, the most prevalent and financially burdensome pain condition, through endogenous opioids. We will test study hypotheses by assessing pain ratings in response to a chronic low back pain-evoking maneuver during mindfulness meditation and infusion of the opioid antagonist, naloxone and saline. If mindfulness-based chronic pain relief is not mediated by endogenous opioids, then the treatment of chronic pain may be deemed more effective with meditation due to a lack of cross-tolerance with traditional therapies and will provide mechanistic insight to target multiple pain conditions.